A research team at Wayne State University School of Medicine found that stress reduced virus resistance and increased susceptibility to COVID-19 in embryonic stem cells and their progeny cells in the yolk sac, a condition that can threaten the early embryo and lead to miscarriages or other side effects Effects.
In “Stress reduces the host’s virus resistance and increases the susceptibility to Covid in embryonic stem cells” (https://link.springer.com/article/10.1007/s12015-021-10188-w), published in Stem Cell Reviews and Reports, Daniel Rappolee, Ph.D., Associate Professor of Obstetrics and Gynecology and the CS Mott Center for Human Growth and Development, reported that controlled hyperosmotic stress can increase COVID-19 susceptibility and decrease virus resistance in an animal model of embryonic stem cells.
Daniel Rappolee, Ph.D.
Of the 30 genontological groups of functionally related genes that the team tested for susceptibility to viruses in the host cell under stress, 15 underwent significant changes. The response from four of these groups suggests that stress decreases resistance to viral attack on embryonic stem cells, while normal differentiation of stem cells increases virus resistance.
The research team also examined the gene expression of known coronavirus receptors and found that the virus receptors of Covid19 / Cov2 / SARS2 as well as earlier Cov1 / SARS1 (2003) and MERS (2012) increase with stress and stress-forced differentiation of embryonic stem cells in the yolk sac.
The researchers used some form of controlled hyperosmotic stress to create stress on the cells. Hyperosmotic stress occurs when more molecules are dissolved in the solution outside the cell than inside the cell, thereby drawing fluid out of the cell.
Stress factors that can trigger a vulnerability can be internal or external in nature, such as dehydration or untreated high blood sugar. Hyperosmotic stress can represent several other environmental stressors that are currently being tested for their ability to make stem cells and embryos more vulnerable and less resistant to coronaviruses.
The stress response can decrease the resistance of embryonic stem cell virus to many other viruses, not just the virus that causes COVID-19, said Dr. Rappolee.
“Stress can increase immediate embryonic lethality and miscarriages or long-term health effects after COVID-19 infection of cells derived from embryonic stem cells shortly after fertilization,” said Dr. Rappolee. “Other stressors that pregnant women are exposed to, including hormonal stress, stress from environmental toxins, dietary supplements, and drugs, should be tested.”
Stressors often do not appear individually, which suggests testing for undesirable effects due to mixtures of stressors, for example hormonal stress that originates in the body and environmental toxins that come from outside the body.
Dr. Rappolee tests categories of potential stressors that arise inside and outside the body for their effects on susceptibility to Covid and coronavirus and host cell resistance.
The research team included Mohammed Abdulhasan, Ph.D., Baghdad University; Ximena Ruden, BS, Research Associate, University of Arizona; Benjamin Rappolee, Washington University of St. Louis; Sudipta Dutta, Ph.D., Texas A&M University; Katherine Gurdziel, Ph.D., of the WSU Genome Sciences Core; Douglas Ruden, Ph.D., Professor of Obstetrics and Gynecology and Director of the WSU Institute of Environmental Health Sciences; Awoniyi Awonuga, MD, professor of obstetrics and gynecology and director of the WSU department of reproductive endocrinology and infertility; Steve Korzeniewski, Ph.D., Associate Professor of Family Medicine and Public Health Sciences; and Elizabeth Puscheck, MD, professor of obstetrics and gynecology.
Interns working towards their bachelor’s or high school diplomas also contributed to this research. These include: Teya Marbens, University of Detroit Mercy, Sterling Heights, who participated in WSU’s ReBuild program, funded by the National Institutes of Health; and Tanmai Nimmagadda, Detroit Country Day School, Northville; Syed Ali, Cass Technical High School, Detroit; and Munsir Jabir, Cass Technical High School, Detroit, who participated in the School of Medicine biomedical career advancement program.
The study was supported by funds from the National Institutes of Health (R41 ES031451, R41 ES028991), the WSU Institute for Environmental Health Sciences, the pilot project of the WSU Center for Urban Responses to Environmental Stressors (P30 ES020957) and the Michigan Emerging Technology Fund.